Comments

Abstract

Animal Models

Upon reading the forum papers we note that “stealth” properties of liposomes apparently still have not been examined extensively in any animal model other than relatively young rodents (mainly mice). The “stealth” concept would be enhanced by studies in species other than mice. If opsonic properties of blood proteins, particularly the presence of naturally-occurring antibodies to phospholipids and cholesterol and resultant complement activation, have any relevance to the removal of liposomes from mouse blood, then it is possible that different liposomes will exhibit “stealth” properties under other circumstances (such as in older mice that often have high titers of antibodies to lipids) or in other animal species. In view of the presumed interest in the commercial exploitation of “stealth” technology it would seem useful to have validating experiments performed in other species, such as dogs, pigs, sheep, and especially in primates.     

Lipid Peroxidation Of L-α -Phosphatidylcholine from Fresh Egg Yolk and from Soybean During Liposome Preparation and Storage

Abstract

Oxidative processes that may occur when susceptible materials like phospholipids are processed and stored should be avoided because they can lead to undesired byproducts. Our attention was focused on the formation of hydroperoxides of conjugated dienes of the esterified polyunsaturated fatty acids that are present in phospholipids. The method used for the evaluation of lipid peroxidation was based on the determination of the “oxidation index”, calculated from UV absorbance. The investigated products were phospholipids of different origin and purity, with and without antioxidants; their autooxidation process was evaluated in the presence of air and under nitrogen. A comparison of the behavior of the various tested products, under the different experimental conditions, indicate how important it is to acquire informations on the autooxidation process for a correct preparation of cosmetic, dermatological or other formulations containing liposomes.     

Guest Editorial

Abstract

It is time that we consider applications of the properties of lipid molecules for other than building grocery bags for carrying therapeutic drugs from the pharmacy to sick cells. Lipids have other functions in the cell besides being components of bilayer-based membranes that separate cellular components. Aside from their role as barriers to diffusion, membranes serve to organize a good deal of cellular chemistry. They also provide lipid molecules that serve to regulate key elements of this chemistry. A great deal of lipid research now focuses on issues related to drug delivery via liposomes. Much of this is published in The Journal of Liposome Research. Is it not time that we “greasers” and this journal point towards lipids as the drugs as well as the drug carriers? The purpose of this brief comment is to review the role of lipids (especially PS) as regulators of cellular chemistry, with special emphasis being placed on the role of PS in regulating blood coagulation.     

Complement-Dependent Phagocytosis of Liposomes: Suppression by “Stealth” Lipids

Abstract

Liposomes containing either ganglioside G_M1, phosphatidylinositol, sulfogalactosyl ceramide, certain other anionic phospholipids, prostaglandin E₂, or thromboxane B₂ have a reduced ability to undergo complement-dependent phagocytosis by cultured macrophages. We propose that this phenomenon is partially responsible for the prolonged circulation time that is observed after intravenous injection of certain liposomes that are said to have “stealth” properties.     

Can S-LCA methodology support responsible sourcing of raw materials in EU policy context?

Purpose

Access, affordability and sustainability of raw material supply chains are crucial to the sustainable development of the European Union (EU) for both society and economy. The study investigates whether and how the social life cycle assessment (S-LCA) methodology can support responsible sourcing of raw materials in Europe. The potential of social indicators already available in an S-LCA database is tested for the development of new metrics to monitor social risks in raw material industries at EU policy level.

Methods

The Product Social Impact Life Cycle Assessment (PSILCA) database was identified as a data and indicators source to assess social risks in raw material industries in EU-28 and extra-EU countries. Six raw material country sectors in the scope of the European policy on raw materials were identified and aggregated among those available in PSILCA. The selection of indicators for the assessment was based on the RACER (Relevance, Acceptance, Credibility, Ease, Robustness) analysis, leading to the proposal of 9 social impact categories. An S-LCA of the selected raw material industries was, thus, performed for the EU-28 region, followed by a contribution analysis to detect direct and indirect impacts and investigate related supply chains. Finally, the social performance of raw material sectors in EU-28 was compared with that of six extra-EU countries.

Results and discussion

Considering the overall social risks in raw material industries, “Corruption”, “Fair salary”, “Health and safety” and “Freedom of association and collective bargaining” emerged as the most significant categories both in EU and extra-EU. EU-28 shows an above-average performance where the only exception is represented by the mining and quarrying sector. An investigation of the most contributing processes to social impact categories for EU-28 led to the identification of important risks originating in the supply chain and in extra-EU areas. Therefore, the S-LCA methodology confirmed the potential of a life cycle perspective to detect burdens shifting and trade-offs. However, only a limited view on the sectoral social performance could be obtained from the research due to a lack of social data.

Conclusions

The S-LCA methodology and indicators appear appropriate to perform an initial social sustainability screening, thus enabling the identification of hotspots in raw material supply chains and the prioritization of areas of action in EU policies. Further methodological developments in the S-LCA field are necessary to make the approach proposed in the paper fully adequate to support EU policies on raw materials.

     

Interferon incorporated into liposomes. A method for the design of homologous and heterologous liposomes and the control of their in-vivo permeability]

The specific features of the fatty acid composition of phospholipid carriers obtained from raw materials of vegetable and animal origin were studied. Differences in the enrichment of phospholipids of different origin with polyene fatty acids were shown. The method for obtaining fluoroliposomes incorporating such components as phospholipids of mouse organs, egg yolk, etc. were proposed. The study proved that the homology of the lipid base of liposomes facilitated their binding by tropic organs and more rapid liberation of the blood stream from them. The selection of lipid carriers and their sources was determined by their uniformity, morpho-functional importance, phospholipid and fatty acid composition, as well as their homology as regards their composition features.     

透明质酸修饰的绿原酸脂质体对U14宫颈癌荷瘤小鼠的抑制作用

目的:对透明质酸(HA)靶向绿原酸(CA)脂质体(HA-CA脂质体)进行处方筛选,以及对U14宫颈癌小鼠的抑制作用实验。方法:筛选制备HA-CA脂质体的方法,并以磷脂比、药脂比、PBS的p H为单因素考察指标通过正交实验筛选最优处方;采用透析袋法考察HA-CA的体外释放;Bal b/c小鼠右腋皮下接种U14宫颈癌瘤株,连续尾静脉注射给药14 d后,摘取瘤体称重,并计算肿瘤生长抑制。结果:采用薄膜分散法制备脂质体,最优处方为磷脂比为4:1,药脂比为1:30,PBS的p H为7.4。HA-CA脂质体与CA脂质体释放曲线基本一致,都具有一定的缓释效果。48 h时,HA-CA脂质体和CA脂质体的累计释放度分别为78.39%、83.01%。HA-CA脂质体对U14宫颈癌小鼠的抑瘤率为60.39%,与阳性对照组环磷酰胺相当,高于CA和CA脂质体。结论:HA-CA脂质体由于其具有主动靶向配体HA的修饰,使其抑制U14宫颈癌裸鼠的效果明显高于CA和CA脂质体。     

Liposomes and Skin Tolerance

Abstract

The authors evaluate different situations where there is an increase or a decrease of complexed liposome tolerance on the skin and in particular of the substances they convey. Since liposomes are made of physiological membrane components, namely phospholipids, they are considered as atoxic microspherules, that are non immunogenic and histocompatible when applied to the skin. When produced in the laboratory (synthetic liposomes) the purity and stability of the lipids making up the liposomes must be kept under strict control. Any undesired side effect should not be attributed to the phospholipids as liposomes, but to the substances (both medical and non) that they convey; indeed side effects result from the interaction and activity of these active principles. On the other hand, the drugs or active principles delivered to the skin by the liposomes have a longer and more concentrated effect and they enter into the systemic circulation in very small amounts, and consequently local and general tolerance is very much enhanced.     

Virus Meets Liposome

Abstract

Sendai virus was the first virus to encounter liposomes. Gangliosides when incorporated into liposomes act as Sendai virus receptors even at 0–4°C. When receptor-containing liposomes are incubated with virus at 37°C, they envelop the virus. At 37°C liposomes also fuse with Sendai virus membrane.

Virus binding initially involves weak adhesion, which may allow the virus to “browse” the cell, and which is followed by adhesion strengthening. MicrogrΔpHs of Sendai virus fusion with liposomes after one minute at 37°C indicate that fusion occurs at the very curved leading edge of the region of the liposome enveloping virus. A model of fusion is proposed that emphasizes the role of the curvature and membrane tension in this localized region of “host” membrane. The curvature assists close approach and destabilizes the outer monolayer. The proposed intermediates are consistent with the “stalk” hypothesis.     

Toward an Overall Analytical Framework for the Integrated Sustainability Assessment of the Production and Supply of Raw Materials and Primary Energy Carriers

The sustainable production and supply of raw materials (“nonenergy raw materials”) and primary energy carriers (“energy raw materials”) is a core element of many policies. The natural resource base for their production and supply, and the access thereto, are limited. Moreover, raw material supply is high on environmental and social impact agendas as well. A broad, quantitative framework that supports decision makers is recommended so as to make use of raw materials and primary energy carriers more sustainably. First, this article proposes a holistic classification of raw materials and primary energy carriers. This is an essential prerequisite for developing an integrated sustainability assessment framework (ISAF). Indeed, frequently, only a subset of raw materials and primary energy carriers are considered in terms of their source, sector, or final application. Here, 85 raw materials and 30 primary energy carriers overall are identified and grouped into seven and five subgroups, respectively. Next, this article proposes a quantitative ISAF for the production and supply of raw materials and primary energy carriers, covering all the sustainability pillars. With the goal of comprehensiveness, the proposed ISAF integrates sustainability issues that have been covered and modeled in quite different quantitative frameworks: ecosystem services; classical life cycle assessment (LCA); social LCA; resource criticality assessment; and particular international concerns (e.g., conflict minerals assessment). The resulting four areas of concerns (i.e., environmental, technical, economic, and social/societal) are grouped into ten specific sustainability concerns. Finally, these concerns are quantified through 15 indicators, enabling the quantitative sustainability assessment of the production and supply of raw materials and primary energy carriers.     

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

Abstract

The COST Action CM1201 “Biomimetic Radical Chemistry” has been active since December 2012 for 4 years, developing research topics organized into four working groups: WG1 – Radical Enzymes, WG2 – Models of DNA damage and consequences, WG3 – Membrane stress, signalling and defenses, and WG4 – Bio-inspired synthetic strategies. International collaborations have been established among the participating 80 research groups with brilliant interdisciplinary achievements. Free radical research with a biomimetic approach has been realized in the COST Action and are summarized in this overview by the four WG leaders.     

Bioactive compounds from brown seaweeds: Phloroglucinol,fucoxanthin and fucoidan as promising therapeutic agents against breast cancer

Breast cancer is one of the most common cancers among women and its incidence tends to increase year by year. Chemotherapy is an effective treatment for many types of cancer, however its toxicity in normal cells and acquired tumor resistance to the drug used are considered as the main barriers. New strategies have been proposed to increase the success of anticancer drugs namely it combination with natural dietary compounds, decreasing drug dose administered and reducing its toxicity to normal cells. Seaweeds are rich in bioactive compounds and, in Traditional Chinese Medicine and Japanese folk medicine are used to “treat” tumors. Attending to the attractive biological effects of some seaweed several efforts have been made to isolate the bioactive compounds and explore its action mechanisms. Phloroglucinol, fucoxanthin and fucoidan are bioactive compounds present in brown seaweed showing chemopreventive and chemotherapeutic effects against cancer. Several mechanisms namely antioxidant, cell cycle arrest, induction of cell death and inhibition of metastasis and angiogenesis have been mentioned as responsible for it anticancer activity. Beside the promising biological effects of these compounds, synergistic effects with cytotoxic drugs have been less explored. This review focuses on the potential protective and therapeutic effect – mainly against breast cancer – of the bioactive compounds phloroglucinol, fucoxanthin and fucoidan present in the brown seaweeds. Current knowledge about interaction between each of these compounds and the conventional anticancer drugs and the further research opportunities are discussed.     

Gendering ethnic conflicts: minority women in divided societies – the case of Muslim women in India

ABSTRACT

This article explores the practical and theoretical significance and long-term consequences of the failure to incorporate women’s interests in post-conflict negotiations by examining the case of Muslim women in India. Analyses of deeply divided societies must recognize that political competition and political violence do not affect all citizens equally. Also, the “larger picture” depicted by inter-community conflicts should not overshadow the effects of intra-community conflicts, which are no less important. Evident within each community conflict are the winners and the losers of the political accommodation process, in which the marginalized and weaker sections of each “side” of the conflict may be the real “losers”. Gendered analysis of ethnic conflicts and ethnic conflict resolution demands a reorientation of the concepts of conflict and security – Whose conflict is being solved and who is being secured?     

Long-Circulating Liposomes: Development and Perspectives

Abstract

Long-circulating liposomes can be prepared by coating liposome surface with a hydrophilic layer of oligosaccharides, glycoproteins, polysaccharides and synthetic polymers in order to make liposomes “invisible” for scavenger cells of the mononuclear phagocyte system. Incorporation of lipid-anchored poly(ethylene glycol) in liposome bilayer allows to prolong its circulation at least tenfold. Various designs of glycolipid- and polymer-based liposomes are presented, possible mechanisms of action are discussed; potential of these liposomes for drug targeting is presented.     

Why do Polyethylene Glycol-Coated Liposomes Circulate So Long?: Molecular Mechanism of Liposome Steric Protection with Polyethylene Glycol: Role of Polymer Chain Flexibility

Abstract

The hypothesis is suggested describing the molecular mechanism of protective action of poly(ethylene glycol) on liposomes in vivo on the basis of polymer properties in solvent. The protective layer of polymer on the liposome surface is considered as a “cloud” of possible conformations of macromolecules. If polymer is water-soluble and has flexible main chain, the density of this cloud is high enough to prevent the interaction of opsonins with liposome. At the same time, certain optimal concentration of the protective polymer can be found, when more loose areas in polymeric “clouds” can be used for the immobilization of antibodies on liposomes. As a result, long-circulating targeted liposomes can be obtained.     

Transfer of a lipophilic drug (temoporfin) between small unilamellar liposomes and human plasma proteins: influence of membrane composition on vesicle integrity and release characteristics

Abstract

The introduction of PEG lipid conjugates into lipid bilayers leads to long circulating liposomes with improved pharmacokinetics and pharmacodynamics characteristics. The concentration range of PEG-lipids is limited by their micelle forming properties. We investigated two phosphatidyl oligoglycerols as potential alternatives to PEG-lipid conjugates and compared their micelle forming properties after incorporation of increasing amounts of oligoglycerols into gel-phase liposomes via cryo-transmission electron microscopy. The incorporation of highly hydrophobic drugs into liposomes makes water soluble formulations possible and improves the therapeutic properties of the drug. We incorporated the hydrophobic photosensitizer temoporfin into liposomes varying in membrane fluidity and nature of surface modifying agents. The main purpose of this study was the investigation of liposome integrity and temoporfin incorporation stability in the presence of plasma. After incubation of temoporfin-loaded liposomes with human plasma for different time intervals, liposomes and the single lipoprotein fractions were separated via size-exclusion chromatography. Liposome stability and temoporfin distribution profile over the lipoprotein fractions were determined with the help of a non-exchangeable ³H-lipid label and ¹⁴C-labeled temoporfin. The results demonstrate that both oligoglycerols are suitable alternatives to PEG-lipid conjugates because of the lack of micelle forming properties, comparable liposome stability, and a reduced temoporfin transfer rate compared to PEG-lipids. Furthermore, the incorporation stability of temoporfin is – at least to some extent – influenced by membrane fluidity, indicating that fluid membranes may be better suited for retention of lipophilic drugs.     

Application of “spider-web” mode in discovery and identification of Q-markers from Xuefu Zhuyu capsule

BackgroundThe selection of quality control indicators in a complex system is a key scientific issue for the study of Chinese materia medica (CMM), which is directly related to its safety and efficacy. In order to scientifically understand and control the quality of CMM, quality marker (Q-marker) has been recently raised as a new concept, which provided a novel research idea for the quality control and evaluation of CMM.PurposeBy a new and integrated “spider-web” mode, Q-markers of Xuefu Zhuyu capsule (XZC) were comprehensively uncovered, conducing to great improvement of quality control of XZC.MethodsMainly established by three dimensions derived from six variables including content, stability and activity, “spider-web” mode was constructed to evaluate Q-marker property of candidate compounds by taking regression area of the tested compounds into account.ResultsThe candidate compounds with larger regression area were preferentially adopted as Q-markers, which should possess the satisfactorily integrated properties of content, stability and activity. Six compounds, naringin, isoliquiritin, paeoniflorin, protocatechuic acid, neohesperidin and ferulic acid, were identified and preferred as Q-markers of XZC.ConclusionBased on “spider-web” mode, Q-markers from Xuefu Zhuyu capsule were successfully screened, which would substantially perform quality control of XZC and prove the feasibility of “spider-web” mode in solving the selection of quality control indicators from compound formulae.     

Diospyros melanoxylon,a bread-winner tree of India

This endemic plant of India and Ceylon is used in various ways. Besides being the source of Indian ebony, its wood is also utilized for making boxes, combs, ploughs and beams. The fruits are eaten and sold commercially. The bark is burnt by tribals to “cure” small-pox. The seeds are prescribed as cure for mental disorders, palpitation of heart and nervous breakdown. Above all, the leaves of this plant constitute one of the most important raw materials of the “Bidi” (Indian cheap smoke) industry.     

Commentary: Rantosomes and Ravosomes

Abstract

Those who cannot remember the past are condemned to repeat it.—George Santayana

I am fortunate to have entered the liposome research field in its infancy. In that “golden age” of liposome research, scientific advances related to lipid vesicles appeared in the literature on a regular basis and there was little danger of repeating a study because there was so little published. Many of the potential uses of liposomes in drug delivery that have come to be, were discussed in two creative and prescient articles published in 1976 in the New England Journal of Medicine by Gregory Gregoriadis (1). At liposome/ drug carrier meetings, discussions raged over materials, mechanisms, models, methods and structures. My colleagues and I published a few papers dealing with liposome preparation and extrusion through polycarbonate membranes to form defined diameter populations of liposomes (2-4). The extrusion method is widely used and like the original Bangham method (5) for making MLV, it has become so a part of making liposomes that it is no longer cited. For those entering the liposome field the failure to correctly attribute is understandable, given the vast number of liposome publications (Table 1) that have appeared over the ensuing years.